title: Sol-gel silica controlled release thin films for the inhibition of methicillin-resistant Staphylococcus aureus.
abstract: The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection has significantly increased. Generally, the success of this bacterium as a pathogen is attributed to its ability to adhere to surfaces and remain there, under the protection of an extracellular matrix known as biofilm. To combat MRSA with regular doses of vancomycin, efforts are continuously underway to increase its effectiveness. A promising technique is to use combinational therapeutics. In vitro experiments showed that farnesol can be used as an adjuvant with conventional antibiotics. Farnesol is a natural sesquiterpenoid and quorum-sensing molecule. The biggest obstacle to using this concept is that farnesol is highly water insoluble. This compromises its bioavailability if it were to be used along with vancomycin at the site of infection when the treatment needs to be administered in vivo. Herein we designed an efficient therapeutic strategy for the simultaneous delivery of both antibiotic and adjuvant in order to treat MRSA infections. We demonstrate that sufficient quantities of both vancomycin and farnesol can be incorporated into sol-gel silica applied as thin films on an implant surface. The incorporation of the hydrophobic farnesol does not affect the stability of the thin films and neither does it affect the controlled release of vancomycin. The data demonstrate the potent adjuvant effect of farnesol on vancomycin in inhibiting MRSA infection. In vitro experiments show the complete inhibition (10(6) fold reduction in growth compared to control) of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) when the ratio of vancomycin to farnesol in the sol-gel silica films is optimized. The local delivery of antibiotics minimizes the need for systemic antibiotics. The incorporation of vancomycin and farnesol into thin sol-gel films represents a new treatment paradigm for the topical delivery of antibiotics with adjuvant. The potential clinical benefits are significant and include avoiding the need for revision surgery, preventing surgical site infection and controlling healthcare costs.
authors.affiliation: Center for Bioactive Materials and Tissue Engineering, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Ashwin
authors.initials: A
authors.lastname: Agrawal
authors.forename: Christine
authors.initials: C
authors.lastname: Knabe
authors.forename: Paul
authors.initials: P
authors.lastname: Ducheyne
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005204:Farnesol / Q000494:pharmacology*; D005782:Gels; D057927:Hydrophobic and Hydrophilic Interactions; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D012822:Silicon Dioxide / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005782:Gels; D005204:Farnesol; D014640:Vancomycin; D012822:Silicon Dioxide
keywords: Antibiotics; Controlled release; Drug delivery; Implant; MRSA; Sol–gel silica